Chronic opioid use is associated with neurocognitive dysfunction and neurodegeneration in humans. However, the cellular mechanisms of opioids as a risk factor for neurodegeneration need clarification. My research investigates how the dysfunctional signaling induced by chronic opioid use can contribute to neurodegeneration. Chronic opioid use decreases the expression and function of ATP-sensitive potassium channels (KATP) and paradoxically increase cyclic adenylyl monophosphate (cAMP signaling). KATP channels transform metabolic cues in energy-hungry neurons into electrical potential. Metabolic dysfunction and hyper excitability are two hallmarks of neurodegenerative diseases. Specifically, I am investigating how the EPAC protein from cAMP signaling interacts with KATP channels biochemically and functionally through a human neuroblastoma model. Ultimately, my work aims to create treatment for opioid use disorders against the neurotoxic effects and improve treatment of neurodegenerative disease.

Amanda H. Klein, PhD